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Phylogenomic analysis reveals extensive phylogenetic mosaicism in the Human GPCR Superfamily\ud

By Robin G. Allaby and Mathew Woodwark

Abstract

A novel high throughput phylogenomic analysis (HTP) was applied to the rhodopsin G-protein coupled receptor (GPCR) family. Instances of phylogenetic mosaicism between receptors were found to be frequent, often as instances of correlated mosaicism and repeated mosaicism. A null data set was constructed with the same phylogenetic topology as the rhodopsin GPCRs. Comparison of the two data sets revealed that mosaicism was found in GPCRs in a higher frequency than would be expected by homoplasy or the effects of topology alone. Various evolutionary models of differential conservation, recombination and homoplasy are explored which could result in the patterns observed in this analysis. We find that the results are most consistent with frequent recombination events. A complex evolutionary history is illustrated in which it is likely frequent recombination has endowed GPCRs with new functions. The pattern of mosaicism is shown to be informative for functional prediction for orphan receptors. HTP analysis is complementary to conventional phylogenomic analyses revealing mosaicism that would not otherwise have been detectable through conventional phylogenetics

Topics: QH426
Publisher: Libertas Academica Ltd.
Year: 2007
OAI identifier: oai:wrap.warwick.ac.uk:716

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  1. (2004). Phylogenetics in the bioinformatics culture of understanding. doi
  2. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. doi
  3. (2003). The Evolution of MRG, a neuron-specifi c gene family implicated in nociception. doi
  4. (2001). A diverse family of GPCRs Expressed in specifi c subsets of nociceptive sensory neurons. doi
  5. (2003). Phylogenomics: Intersection of evolution and genomics. doi
  6. (1998). Phylogenomics: Improving functional predictions for uncharacterised genes by evolutionary analysis. doi
  7. (1989). PHYLIP—Phylogeny Inference Package (version 3.2). Cladistics, doi
  8. (1999). Modelling G-protein-coupled receptors for drug design. doi
  9. The G-protein coupled receptors in the human genome form fi ve main families. Phylogenetic analysis, paralogon groups and fi ngerprints. doi
  10. (1997). PSeq-Gen: an application for the Monte Carlo simulation of protein sequence evolution along phylogenetic trees. doi
  11. (2001). Orphan G-protein-coupled receptors and natural ligand discovery. Trends Pharm. doi
  12. (2002). Activation of orphan receptors by the hormone relaxin. doi
  13. (1992). The rapid generation of mutation data matrices from protein sequences. doi
  14. (2002). Phylogenetic analysis of 277 human Gprotein-coupled receptors as a tool for the prediction of orphan receptor ligands. Genome Biology,
  15. (2001). Evolutionary analysis of the human genome. doi
  16. (2003). Identifi cation of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein coupled receptor GPCR135. doi
  17. (2003). Mesquite: a modular system for evolutionary analysis.
  18. (2000). T-Coffee: A novel method for fast and accurate multiple sequence alignment. doi
  19. (1999). Genome evolution and the evolution of exon shuffl ing—a review. doi
  20. (2000). Gene conversion among chemokine receptors. doi
  21. (2004). Structural determinants of allosteric ligand activation in RXR heterodimers. doi
  22. (2004). Phylogenomic inference of protein molecular function: advances and challenges. doi
  23. (1996). Dirichlet mixtures: a method of improved detection of weak but signifi cant protein sequence homology. doi
  24. (2003). Characterisation of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. doi
  25. (1994). CLUSTALW: improving the sensitivity of progressive sequence alignment through sequence weighting, position specifi c gap-penalties and weight matrix choice. doi
  26. Allaby and Woodwark Evolutionary Bioinformatics 2007: 3 Supplementary Materials Supplementary alignments Supplementary Data Supplementary Figure 1. Supplementary Figure 2. Supplementary Tables doi

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